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Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies

Study of the association between single nucleotide polymorphisms (SNPs) of methotrexate (MTX) pathway genes and MTX-related toxicity in the treatment of hematological malignancies is popular. Here, we studied the association between SNPs of MTHFR and ABCB1 and MTX-related toxicity in 157 adult Chine...

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Detalles Bibliográficos
Autores principales: Han, Jian, Liu, Lu, Meng, Li, Guo, Huan, Zhang, Jin, Han, Zhi-Qiang, Hong, Zhen-Ya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739189/
https://www.ncbi.nlm.nih.gov/pubmed/35004279
http://dx.doi.org/10.3389/fonc.2021.759805
Descripción
Sumario:Study of the association between single nucleotide polymorphisms (SNPs) of methotrexate (MTX) pathway genes and MTX-related toxicity in the treatment of hematological malignancies is popular. Here, we studied the association between SNPs of MTHFR and ABCB1 and MTX-related toxicity in 157 adult Chinese patients diagnosed with hematological malignancies. Patients were genotyped for MTHFR rs1801131, MTHFR rs1801133, and ABCB1 rs1045642 by fluorescence in situ hybridization. Patients with MTHFR rs1801133T allele had a significantly higher risk of hematopoietic toxicity compared with those with CC genotype (p=0.003). With respect to MTHFR rs1801131, patients with CC and AC genotypes had significantly lower frequency of hematopoietic toxicity than patients with AA genotype (p=0.044). In conclusion, we identified an important influence of the SNPs of ABCB1 and MTHFR on MTX-related hematopoietic toxicity in adults with hematological malignancies. To optimize high-dose (HD)-MTX therapy and reduce related hematopoietic toxicity, it is necessary to detect the SNPs of MTHFR and ABCB1 before initiating HD-MTX and deciding the optimal dose of MTX and duration of leucovorin rescue, according to genetic tests and disease type in adults with hematological malignancies.